Bacterial vaginosis (BV) is a common cause of vaginitis and increases women's risk of pelvic inflammatory disease, adverse pregnancy outcomes, and risk of HIV acquisition. The etiology of BV is unclear, though it is believed to involve loss of vaginal hydrogen peroxide-producing lactobacilli and acquisition of complex bacterial communities that include many fastidious BV- associated bacteria (BVAB) that have recently been detected using PCR methods. Treatment failure (persistence) is common, and may be facilitated by unprotected sex. We propose to intensively characterize the vaginal microbiota of heterosexual women with BV using molecular tools pre- and post-treatment, and assess for the presence of select Toll-like receptor (TLR) polymorphisms in women with BV pre- treatment. We will also assess the male sex partners of these women for presence and duration of genital colonization with BVAB, and assess the effect of eradication of key BVAB (and BV) in female partners and condom use on BVAB colonization in the male partner. The proposed work will allow us to add to our knowledge base of antimicrobial resistance as a mechanism for persistent BV, and to examine potential contributions to BV and BV persistence of (1) the male partner as a reservoir for BVAB, and how this is affected by successful treatment of BV;(2) reported sexual practices, including male partners'condom use;and (3) TLR profiles as measured by single nucleotide polymorphisms (SNP). We hypothesize that detection of specific BVAB in the Clostridiales Order will (1) predict BV persistence when detected pre-treatment, (2) be detected more frequently in men whose female partners have BV than in men whose partners have no BV, and (3) be associated with unprotected sexual behavior and failure of BV to resolve in women, supporting the hypothesis that BVAB colonization of male genitalia may serve as a reservoir for re-infection of female partners. We also predict that women's likelihood of BV will be associated with specific TLR2 and TLR4 polymorphisms, and these will also be associated with BV persistence. Our overall goal is to combine human genetic studies with detailed microbiologic and behavioral assessment of women with and without BV and their male partners to elucidate the pathogenesis of BV.